Using generalized additive models to decompose time series and waveforms, and dissect heart-lung interaction physiology.

Common physiological time series and waveforms are composed of repeating cardiac and respiratory cycles. Often, the cardiac effect is the primary interest, but for, e.g., fluid responsiveness prediction, the respiratory effect on arterial blood pressure also convey important information. In either case, it is relevant to disentangle the two effects. Generalized additive models (GAMs) allow estimating the effect of predictors as nonlinear, smooth functions. These smooth functions can represent the cardiac and respiratory cycles' effects on a physiological signal. We demonstrate how GAMs allow a decomposition of physiological signals from mechanically ventilated subjects into separate effects of the cardiac and respiratory cycles. Two examples are presented. The first is a model of the respiratory variation in pulse pressure. The second demonstrates how a central venous pressure waveform can be decomposed into a cardiac effect, a respiratory effect and the interaction between the two cycles. Generalized additive models provide an intuitive and flexible approach to modelling the repeating, smooth, patterns common in medical monitoring data.

Performance of the Hypotension Prediction Index May Be Overestimated Due to Selection Bias.

The Hypotension Prediction Index is a proprietary prediction model incorporated into a commercially available intraoperative hemodynamic monitoring system. The Hypotension Prediction Index uses multiple features of the arterial blood pressure waveform to predict hypotension. The index publication introducing the Hypotension Prediction Index describes the selection of training and validation data. Although precise details of the Hypotension Prediction Index algorithm are proprietary, the authors describe a selection process whereby a mean arterial pressure (MAP) less than 75 mmHg will always predict hypotension. We hypothesize that the data selection process introduced a systematic bias that resulted in an overestimation of the current MAP value's ability to predict future hypotension. Since current MAP is a predictive variable contributing to Hypotension Prediction Index, this exaggerated predictive performance likely also applies to the corresponding Hypotension Prediction Index value. Other existing validation studies appear similarly problematic, suggesting that additional validation work and, potentially, updates to the Hypotension Prediction Index model may be necessary.

Existing fluid responsiveness studies using the mini-fluid challenge may be misleading: Methodological considerations and simulations.

BACKGROUND: The mini-fluid challenge (MFC) is a clinical concept of predicting fluid responsiveness by rapidly infusing a small amount of intravenous fluids, typically 100 ml, and systematically assessing its haemodynamic effect. The MFC method is meant to predict if a patient will respond to a subsequent, larger fluid challenge, typically another 400 ml, with a significant increase in stroke volume. METHODS: We critically evaluated the general methodology of MFC studies, with statistical considerations, secondary analysis of an existing study and simulations. RESULTS: Secondary analysis of an existing study showed that the MFC could predict the total fluid response (MFC + 400 ml) with an area under the receiver operator characteristic curve (AUROC) of 0.92, but that the prediction was worse than random for the response to the remaining 400 ml (AUROC = 0.33). In a null simulation with no response to both the MFC and the subsequent fluid challenge, the commonly used analysis could predict fluid responsiveness with an AUROC of 0.73. CONCLUSION: Many existing MFC studies are likely overestimating the classification accuracy of the MFC. This should be considered before adopting the MFC into clinical practice. A better study design includes a second, independent measurement of stroke volume after the MFC. This measurement serves as reference for the response to the subsequent fluid challenge.

Changes in arterial blood pressure characteristics following an extrasystolic beat or a fast 50 ml fluid challenge do not predict fluid responsiveness during cardiac surgery.

Prediction of fluid responsiveness is essential in perioperative goal directed therapy, but dynamic tests of fluid responsiveness are not applicable during open-chest surgery. We hypothesised that two methods could predict fluid responsiveness during cardiac surgery based on their ability to alter preload and thereby induce changes in arterial blood pressure characteristics: (1) the change caused by extrasystolic beats and (2) the change caused by a fast infusion of 50 ml crystalloid (micro-fluid challenge). Arterial blood pressure and electrocardiogram waveforms were collected during surgical preparation of the left internal mammary artery in patients undergoing coronary artery bypass surgery. Patients received a fluid challenge (5 ml/kg ideal body weight). The first 50 ml were infused in 10 s and comprised the micro-fluid challenge. Predictor variables were defined as post-ectopic beat changes (compared with sinus beats preceding ectopy) in arterial blood pressure characteristics, such as pulse pressure and systolic pressure, or micro-fluid challenge induced changes in the same blood pressure characteristics. Patients were considered fluid responsive if stroke volume index increased by 15% or more after the full fluid challenge. Diagnostic accuracy was calculated by the area under the receiver operating characteristics curve (AUC). Fifty-six patients were included for statistical analysis. Thirty-one had extrasystoles. The maximal AUC was found for the extrasystolic change in pulse pressure and was 0.70 (CI [0.35 to 1.00]). The micro-fluid challenge method generally produced lower AUC point estimates. Extrasystoles did not predict fluid responsiveness with convincing accuracy in patients undergoing cardiac surgery and changes in arterial waveform indices following a micro-fluid challenge could not predict fluid responsiveness. Given a low number of fluid responders and inherently reduced statistical power, our data does not support firm conclusions about the utility of the extrasystolic method. CLINICAL TRIAL REGISTRATION: Unique identifier: NCT02903316. https://clinicaltrials.gov/ct2/show/NCT02903316?cond=NCT02903316&rank=1 .

The response of a standardized fluid challenge during cardiac surgery on cerebral oxygen saturation measured with near-infrared spectroscopy.

Near infrared spectroscopy (NIRS) has been used to evaluate regional cerebral tissue oxygen saturation (ScO2) during the last decades. Perioperative management algorithms advocate to maintain ScO2, by maintaining or increasing cardiac output (CO), e.g. with fluid infusion. We hypothesized that ScO2 would increase in responders to a standardized fluid challenge (FC) and that the relative changes in CO and ScO2 would correlate. This study is a retrospective substudy of the FLuid Responsiveness Prediction Using Extra Systoles (FLEX) trial. In the FLEX trial, patients were administered two standardized FCs (5 mL/kg ideal body weight each) during cardiac surgery. NIRS monitoring was used during the intraoperative period and CO was monitored continuously. Patients were considered responders if stroke volume increased more than 10% following FC. Datasets from 29 non-responders and 27 responders to FC were available for analysis. Relative changes of ScO2 did not change significantly in non-responders (mean difference - 0.3% ± 2.3%, p = 0.534) or in fluid responders (mean difference 1.6% ± 4.6%, p = 0.088). Relative changes in CO and ScO2 correlated significantly, p = 0.027. Increasing CO by fluid did not change cerebral oxygenation. Despite this, relative changes in CO correlated to relative changes in ScO2. However, the clinical impact of the present observations is unclear, and the results must be interpreted with caution.Trial registration:http://ClinicalTrial.gov identifier for main study (FLuid Responsiveness Prediction Using Extra Systoles-FLEX): NCT03002129.

Automated echocardiography for measuring and tracking cardiac output after cardiac surgery: a validation study.

Echocardiographic measurement of cardiac output with automated software analyses of spectral curves in the left ventricular outflow tract has been introduced. This study aimed to assess the precision and accuracy of cardiac output measurements as well as the ability to track cardiac output changes over time comparing the automated echocardiographic method with the continuous pulmonary artery thermodilution cardiac output technique and the manual echocardiographic method in cardiac surgery patients. Cardiac output was measured simultaneously with all three methods in 50 patients on the morning after cardiac surgery. A second comparison was performed 90-180 min later. Precisions for each method were measured. Bias and limits of agreement (LoA) between methods were assessed and concordance- and polar plots were used for evaluating trending of cardiac output. When comparing the automated echocardiographic method with the thermodilution technique, the mean bias was 0.72 L/min with LoA - 1.89; 3.33 L/min corresponding to a percentage error of 46%. The concordance rate was 47%. The mean bias between the automated- and the manual echocardiographic methods was - 0.06 L/min (95% LoA - 2.33; 2.21 L/min, percentage error 42%). The concordance rate was 79%. The automated echocardiographic method did not meet the criteria for interchangeability with the thermodilution technique or the manual echocardiographic method. Trending ability was poor when compared to the continuous thermodilution technique, but moderate when compared to the manual echocardiographic method.Trial registry number: NCT03372863. Retrospectively registered December 14th 2017.

Journal of clinical monitoring and computing end of year summary 2018: hemodynamic monitoring and management.

Hemodynamic management is a mainstay of patient care in the operating room and intensive care unit (ICU). In order to optimize patient treatment, researchers investigate monitoring technologies, cardiovascular (patho-) physiology, and hemodynamic treatment strategies. The Journal of Clinical Monitoring and Computing (JCMC) is a well-established and recognized platform for publishing research in this field. In this review, we highlight recent advancements and summarize selected papers published in the JCMC in 2018 related to hemodynamic monitoring and management.

Using extra systoles and the micro-fluid challenge to predict fluid responsiveness during cardiac surgery.

Fluid responsiveness prediction is difficult during cardiac surgery. The micro-fluid challenge (micro-FC; rapid central infusion of 50 ml) and the extrasystolic method utilising post-extrasystolic preload increases may predict fluid responsiveness. Two study windows during coronary artery bypass graft surgery were defined, 1: After anaesthesia induction until surgical incision, 2: Left internal mammarian artery surgical preparation period. Each window consisted of 10-15 min observation for extrasystoles before a micro-FC was performed, after which a traditional fluid challenge (FC) was performed (5 ml/kg). Extrasystolic and micro-FC induced changes in hemodynamic variables were derived as predictors of fluid responsiveness defined as stroke volume increasing > 10% following FC. 61 patients were studied. Post-ectopic changes in pulse pressure (PP) predicted fluid responsiveness with receiver operating characteristic area (AUC) of 0.69 [CI 0.40;0.97] in the first study window and 0.64 [0.44;0.86] in the second window. Other post-ectopic predictors such as pre-ejection period (PEP) and systolic blood pressure (SBP) had similar or lower AUCs. Heart rate was 52.9 (SD ±8.4) min- 1 and 53.6 (± 8.8) min- 1 in the two study windows. Micro-FC induced changes in PEP had AUC of 0.74 [0.57;0.90] in the first window and 0.60 [0.40;0.76] in the second window. Correcting micro-FC induced changes in PEP for the micro-FC induced changes in heart rate had AUCs of 0.84 [0.70;0.97] in the first window and 0.63 [0.47;0.79] in the second window. The investigated methods revealed insufficient validity during cardiac surgery. RR interval corrected changes during a micro-FC should be investigated further. Trial registration Clinicaltrials.gov: NCT03002129.

Where are we heading with fluid responsiveness research?

PURPOSE OF REVIEW: Fluid responsiveness prediction is not always possible with well established dynamic approaches such as passive leg raising or pulse pressure variation in the ICU. The purpose of the present review is to summarize emerging alternative techniques for fluid responsiveness prediction in adult critically ill patients and discuss their methodology and applicability. In addition, the future role of fluid responsiveness prediction in the ICU is discussed. RECENT FINDINGS: Several new dynamic techniques have been investigated and they all contribute to the applicability of fluid responsiveness techniques. Although increasing the applicability, most of the emerging techniques still rely on ventilator setting changes in patients that are fully or almost fully adapted to the ventilator or require reliable flow monitoring, which prevents broad applicability. Yet, the mini/micro fluid challenges and the use of extrasystolic preload changes have the potential of being more applicable but all reviewed methods need further validation and methodological refinement. SUMMARY: Emerging techniques are encouraging for broader applicability of fluid responsiveness prediction. Still, the clinical impact of correctly predicting fluid responsiveness remains to be investigated in the critically ill and the research community should have a clear aim of moving toward that type of studies.

INSPIRE, a publicly available research dataset for perioperative medicine.

We present the INSPIRE dataset, a publicly available research dataset in perioperative medicine, which includes approximately 130,000 surgical operations at an academic institution in South Korea over a ten-year period between 2011 and 2020. This comprehensive dataset includes patient characteristics such as age, sex, American Society of Anesthesiologists physical status classification, diagnosis, surgical procedure code, department, and type of anaesthesia. The dataset also includes vital signs in the operating theatre, general wards, and intensive care units (ICUs), laboratory results from six months before admission to six months after discharge, and medication during hospitalisation. Complications include total hospital and ICU length of stay and in-hospital death. We hope this dataset will inspire collaborative research and development in perioperative medicine and serve as a reproducible external validation dataset to improve surgical outcomes.

Ultrasound of the inferior vena cava does not predict hemodynamic response to early hemorrhage.

BACKGROUND: Ultrasonographic evaluation of the inferior vena cava (IVC) provides information on central hemodynamics and predicts fluid responsiveness during positive pressure ventilation. In spontaneously breathing patients, the correlations between IVC dynamics and the hemodynamic response to volume shifts remain to be described. OBJECTIVES: We aimed to describe the correlation between IVC dynamics and the changes in cardiac output (CO) caused by controlled hemorrhage. METHODS: Healthy donors from the blood bank were eligible for inclusion. Measurements of the IVC and CO were performed before and immediately after blood donation using ultrasound methods. A control group served to evaluate the effect of resting. RESULTS: Thirty-seven participants completed the study. IVC collapsibility index (IVC-CI) and IVC end expiratory diameter (IVCe) both changed significantly after blood donation (p < 0.001). The baseline IVC-CI and IVCe did not correlate with the change in CO (p-values ≥ 0.40). The alterations in IVC-CI and IVCe induced by blood donation also did not correlate with the change in CO (p ≥ 0.71). The sensitivities of IVC-CI or IVCe, defined as an increase in IVC-CI and a decrease in IVCe, for picking up any decrease in CO were 81.3% and 84.4%, respectively. In the control group, no effect was seen between measurements. CONCLUSION: IVC-CI and IVCe did not correlate with the magnitude of hemodynamic response to early hemorrhage. The sensitivity of serial IVC measurements was approximately 80% for detecting early blood loss.

Current use of inotropes in circulatory shock.

BACKGROUND: Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock. METHODS: From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions. RESULTS: A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81-90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement). CONCLUSION: Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.

Using an expiratory resistor, arterial pulse pressure variations predict fluid responsiveness during spontaneous breathing: an experimental porcine study.

INTRODUCTION: Fluid responsiveness prediction is difficult in spontaneously breathing patients. Because the swings in intrathoracic pressure are minor during spontaneous breathing, dynamic parameters like pulse pressure variation (PPV) and systolic pressure variation (SPV) are usually small. We hypothesized that during spontaneous breathing, inspiratory and/or expiratory resistors could induce high arterial pressure variations at hypovolemia and low variations at normovolemia and hypervolemia. Furthermore, we hypothesized that SPV and PPV could predict fluid responsiveness under these conditions. METHODS: Eight prone, anesthetized and spontaneously breathing pigs (20 to 25 kg) were subjected to a sequence of 30% hypovolemia, normovolemia, and 20% and 40% hypervolemia. At each volemic level, the pigs breathed in a randomized order either through an inspiratory and/or an expiratory threshold resistor (7.5 cmH2O) or only through the tracheal tube without any resistor. Hemodynamic and respiratory variables were measured during the breathing modes. Fluid responsiveness was defined as a 15% increase in stroke volume (DeltaSV) following fluid loading. RESULTS: Stroke volume was significantly lower at hypovolemia compared with normovolemia, but no differences were found between normovolemia and 20% or 40% hypervolemia. Compared with breathing through no resistor, SPV was magnified by all resistors at hypovolemia whereas there were no changes at normovolemia and hypervolemia. PPV was magnified by the inspiratory resistor and the combined inspiratory and expiratory resistor. Regression analysis of SPV or PPV versus DeltaSV showed the highest R2 (0.83 for SPV and 0.52 for PPV) when the expiratory resistor was applied. The corresponding sensitivity and specificity for prediction of fluid responsiveness were 100% and 100%, respectively, for SPV and 100% and 81%, respectively, for PPV. CONCLUSIONS: Inspiratory and/or expiratory threshold resistors magnified SPV and PPV in spontaneously breathing pigs during hypovolemia. Using the expiratory resistor SPV and PPV predicted fluid responsiveness with good sensitivity and specificity.